- DOTMA-based amides (DOTMAMs) as a platform for the development of PARACEST MRI contrast agents
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A synthetic methodology leading to previously unknown DOTMA-based secondary amides (DOTMAMs) has been developed. Alkylation of cyclen with l-lactic acid-derived pseudohalides was used as a key step affording the alkyl- and aryl-decorated DOTMAMs. Amino acid-decorated DOTMAMs were obtained via peptide coupling between DOTMA and protected amino acids. Metallation of the DOTMAMs ligand with Tm3+ gave complexes exhibiting proximal amide proton based paramagnetic CEST effects at -50 ppm relative to water.
- Suchy,Li,Milne,Bartha,Hudson
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Read Online
- Amide bond formation using an air-stable source of AlMe3
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Synthesis of amides from coupling esters with a range of primary amines can be conveniently achieved in moderate to excellent yields (69-99%) using an air-stable adduct of trimethylaluminium (AlMe3)2·DABCO (DABCO is 1,4-diazobicyclo[2.2.2]octane), referred to as DABAL-Me3. Reactions can be run without requiring the exclusion of atmospheric oxygen or the drying of solvents.
- Novak, Andrew,Humphreys, Luke D.,Walker, Matthew D.,Woodward, Simon
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Read Online
- Stereoselective Pseudomonas cepacia lipase mediated synthesis of α-hydroxyamides
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A new method for the synthesis of α-hydroxyamides via the Pseudomonas cepacia lipase catalyzed amidation of α-hydroxyesters in non-aqueous media is described. Reactivities of α-hydroxy benzyl esters are excellent, resulting in rapid conversions to good yields of α-hydroxyamides, while ethyl and methyl esters react more slowly, and some hindered esters show no reactivity under the conditions studied. Some benzyl esters react stereoselectively, producing excellent yields of asymmetric α-hydroxyamides.
- Adamczyk, Maciej,Grote, Jonathan,Rege, Sushil
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Read Online
- Enzyme-Promoted Asymmetric Tandem Passerini Reaction
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A versatile and highly efficient three-step, one-pot, enzyme-promoted Passerini tandem reaction has been developed. The chemoenzymatic sequence involved simultaneous enzyme catalyzed hydrolysis, subsequent Passerini reaction, and enzymatic kinetic resolution of the Passerini product. This methodology combines the diversity delivered by multicomponent reactions with the selectivity of biocatalysts, which results in efficient synthesis of the target compounds with excellent enantiomeric excesses of up to 99 %. With a small set of substrates, a large library of complex molecules was obtained within a short time by using the developed procedure.
- ??d?o-Dobrowolska, Anna,Koszelewski, Dominik,Paprocki, Daniel,Madej, Arleta,Wilk, Monika,Ostaszewski, Ryszard
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p. 3047 - 3053
(2017/08/14)
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- Amidation of unactivated ester derivatives mediated by trifluoroethanol
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A catalytic amidation protocol mediated by 2,2,2-trifluoroethanol has been developed, facilitating the condensation of unactivated esters and amines, furnishing both secondary and tertiary amides. The complete scope and limitations of the method are described, along with modified conditions for challenging substrates such as acyclic secondary amines and chiral esters with retention of chiral integrity.
- McPherson, Christopher G.,Caldwell, Nicola,Jamieson, Craig,Simpson, Iain,Watson, Allan J. B.
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supporting information
p. 3507 - 3518
(2017/04/26)
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- Amides in one pot from Carboxylic Acids and Amines via Sulfinylamides
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An efficient method has been developed for the direct amidification of carboxylic acids via sulfinylamides preformed in situ by the reaction of pure amines with prop-2- ene-1-sulfinyl chloride. The method can be applied to aliphatic acids, including pivalic acid, aromatic acids, and primary and secondary amines. It is compatible with acids bearing unprotected alcohol, phenol, and ketone moieties and applicable to the synthesis of peptides. It does not induce their a-epimerization.
- Bai, Jianfei,Zambron, Bartosz K.,Vogel, Pierre
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supporting information
p. 604 - 607
(2014/04/03)
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- A [3+3] cyclization strategy for asymmetric synthesis of alkyl substituted piperidine-2-ones using 1,2-cyclic sulfamidates: A formal synthesis of (S)-coniine from l-norvaline
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Regioselective ring-opening reactions of a set of representative 1,2-cyclic sulfamidates with lithium triethylorthopropiolate proceeded efficiently to deliver the corresponding δ-amino-α,β-unsaturated esters after acidic hydrolysis. Hydrogenation of the unsaturated esters and subsequent thermal cyclization afforded the related alkyl substituted piperidine-2-ones. This approach represents a novel [3+3] cyclization strategy for the asymmetric synthesis of alkyl substituted piperidin-2-ones. Efficiency of the cyclization process is illustrated by a formal asymmetric synthesis of (S)-coniine from l-norvaline.
- Karanfil, Abdullah,Balta, Berrin,Eskici, Mustafa
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p. 10218 - 10229,12
(2020/09/02)
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- Kinetic resolution of α-bromoamides: Experimental and theoretical investigation of highly enantioselective reactions catalyzed by haloalkane dehalogenases
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Haloalkane dehalogenases from five sources were heterologously expressed in Escherichia coli, isolated, and tested for their ability to achieve kinetic resolution of racemic α-bromoamides, which are important intermediates used in the preparation of bioactive compounds. To explore the substrate scope, fourteen α-bromoamides, with different Cα- and N-substituents, were synthesized. Catalytic activity towards eight substrates was found, and for five of these compounds the conversion proceeded with a high enantioselectivity (E value >200). In all cases, the (R)-α-bromoamide is the preferred substrate. Conversions on a preparative scale with a catalytic amount of enzyme (enzyme:substrate ratio less 1:50 w/w) were all completed within 17-46 h and optically pure α-bromoamides and α-hydroxyamides were isolated with good yields (31-50%). Substrate docking followed by molecular dynamics simulations indicated that the high enantioselectivity results from differences in the percentage of the time in which the substrate enantiomers are bound favourably for catalysis. For the preferred (R)-substrates, the angle between the attacking aspartate oxygen atom of the enzyme, the attacked carbon atom of the substrate, and the displaced halogen atom, is more often in the optimal range (>157°) for reactivity. This can explain the observed enantioselectivity of LinB dehalogenase in a kinetic resolution experiment.
- Westerbeek, Alja,Szymanski, Wiktor,Wijma, Hein J.,Marrink, Siewert J.,Feringa, Ben L.,Janssen, Dick B.
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experimental part
p. 931 - 944
(2011/06/19)
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- A simple enantioconvergent and chemoenzymatic synthesis of optically active α-substituted amides
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Simple and efficient: The combination of an enzymatic, enantioinverting reaction with simple follow-up processes allows the transformation of readily available racemic compounds into versatile chiral α-substituted amides (see picture; Ms=methanesulfonyl).
- Szymanski, Wiktor,Westerbeek, Alja,Janssen, Dick B.,Feringa, Ben L.
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supporting information; experimental part
p. 10712 - 10715
(2011/12/05)
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- Catalytic asymmetric transfer hydrogenation of ketones using [Ru(p-cymene)Cl2]2 with chiral amino alcohol ligands
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Catalytic asymmetric transfer hydrogenation of aromatic alkyl ketones has been investigated using [Ru(p-cymene)Cl2]2 and new derivatives of β-amino alcohols synthesized from (S)-(-)-lactic acid and mandelic acid as ligands. Chiral secondary alcohols were obtained with good to excellent conversion (60-90%) and moderate to good enantioselectivities (40-86%).
- Deshpande, Sudhindra H.,Kelkar, Ashutosh A.,Gonnade, Rajesh G.,Shingote, Savita K.,Chaudhari, Raghunath V.
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experimental part
p. 231 - 238
(2011/01/12)
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- Synthesis of β-amino alcohols via the reduction of lactamides derived from ethyl (2S)-lactate with borane-methyl sulfide
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Reactions of ethyl (2S)-lactate with various amines affords lactamides that are reduced with borane-methyl sulfide in the presence of boron trifluoride etherate to generate enantiomerically pure β-amino alcohols in good yield. Georg Thieme Verlag Stuttgart.
- Lewis, Frank W.,Eichler, Matthias C.,Grayson, David H.
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experimental part
p. 1923 - 1928
(2009/12/29)
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- FORUMLATIONS
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This invention relates to the use of lactamide compounds of formula (I): CH3CH(OH)C(=O)NR1R2, where R1 and R2 are each independently hydrogen; or C1-6 alkyl, C2-6 alkenyl or C3-6 cycloalkyl, each of which is optionally substituted by up to three substituents independently selected from phenyl, hydroxy, C1-5 alkoxy, morpholinyl and NR3R4 where R3 and R4 are each independently C1-3 alkyl; or phenyl optionally substituted by up to three substituents independently selected from C1-3 alkyl; or R1 and R2 together with the nitrogen atom to which they are attached form a morpholinyl, pyrrolidinyl, piperidinyl or azepanyl ring, each of which is optionally substituted by up to three substituents independently selected from C1-3 alkyl, in formulations to reduce the toxicity associated with other formulation components; to the use of certain lactamide compounds as solvents, especially in formulations, particularly in agrochemical formulations and in environmentally friendly formulations; to novel lactamide compounds; and to processes for preparing lactamide compounds.
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Page/Page column 5-6
(2009/09/25)
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- Trimethylaluminium mediated amide bond formation in a continuous flow microreactor as key to the synthesis of rimonabant and efaproxiral
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A safe, functional-group-tolerant and high-throughput version of the trimethylaluminium mediated amide bond formation reaction has been developed in a microreactor system; rimonabant and efaproxiral were prepared to illustrate the utility of the method. The Royal Society of Chemistry.
- Gustafsson, Tomas,Ponten, Fritiof,Seeberger, Peter H.
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p. 1100 - 1102
(2008/09/21)
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- HETEROCYCLIC MODULATORS OF THE GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-κB ACTIVITY AND USE THEREOF
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Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity including obesity, diabetes, inflammatory and immune diseases, and have the structure of Formula (I) or stereoisomers or prodrugs or solvates or pharmaceutically acceptable salts thereof, wherein A, B, J, K, Z, R, Ra, Rb, Rc, and Rd, are defined herein. Also provided are pharmaceutical compositions and methods of treating obesity, diabetes and inflammatory or immune associated diseases comprising said compounds.
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Page/Page column 69
(2008/06/13)
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- Tricyclic modulators of the glucocorticoid receptor, AP-1, and/or NF-kB activity and use thereof
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Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity including obesity, diabetes, inflammatory and immune diseases, and have the structure of formula (I) or stereoisomers or prodrugs or pharmaceutically acceptable salts thereof, wherein B, J, K, Z, R, Ra, Rb, Rc, Rd, Rq, Rw, m and n are defined herein. Also provided are pharmaceutical compositions and methods of treating obesity, diabetes and inflammatory or immune associated diseases comprising said compounds.
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Page/Page column 37-38
(2008/06/13)
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- Modular evolution of a chiral auxiliary for the 1,3-dipolar cycloaddition of isomuenchnones with vinyl ethers.
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[reaction: see text]. The 1,3-dipolar cycloaddition reaction has long been recognized as a powerful methodology in organic synthesis. More recently, this reaction has become a popular manifold for the construction of chemical diversity. Herein, we report the development of a chiral template for the facially selective cycloaddition of isomuenchnones, a common class of 1,3-dipoles. The modular format of the asymmetric unit allowed a systematic optimization of selectivity. In addition, the chiral auxiliary was removed through an unusually facile ester aminolysis.
- Savinov, Sergey N,Austin, David J
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p. 1415 - 1418
(2007/10/03)
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- Total synthesis of naturally occurring α-tocopherol. Assymetric alkylation and asymmetric epoxidation as means to introduce (R)-configuration at C(2) of the chroman moiety
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Based on the reductive, stereospecific ring closure of (2R,4'R,8'R)-α-'Tocopherylquinone' or corresponding analogues with a short, functionalized side chain (B, Scheme 1) to 1 resp. the chroman system of 1 (C), two different approaches for the introduction of the required tertiary methyl-substituted alcohol structure in the side chain of the aromatic precursors (A, Scheme 1) were developed. The first approach uses asymmetric alkylation in three different versions featuring a) diastereoselective steering with chiral auxiliaries I-IV (Scheme 2) attached as esters to α-keto acids, b) intermediate transfer of chirality in an ester enolate (from 18, Scheme 4) derived from an optically active α-hydroxyacid, c) enantioselective alkylation of phytenal (20) and subsequent ring closure with chirality transfer (Schemes 5-7). The second approach is based on the asymmetric epoxidation of β-metallylalcohol (Sharpless epoxidation), the corresponding epoxyalcohol being converted in situ to the (S)- or (R)-chlorodiol (S)- and (R)-29, respectively, for isolation (Schemes 8 and 9). Nucleophilic epoxide opening with a (3R,7R)-3,7,11-trimethyldodecyl (C15**) and an ArCH2 unit in appropriate sequence is used to assemble the C-framework of the target molecule via corresponding epoxide intermediates from either chlorodiol. Combined with the use of the methoxymethyl-ether function for protection of the hydroquinone system, the epoxide approach provides a short route to 1 (Scheme 10).
- Hubscher,Barner
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p. 1068 - 1086
(2007/10/02)
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- Synthesis and Reaction of Optically Active Morpholinones
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The reactions of variously substituted chiral morpholin-2-and-3-ones chemoselectively synthesized from chiral amino acids and lactic acid as the chiral source are described.
- Kashima, Choji,Harada, Kazuo
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p. 1521 - 1526
(2007/10/02)
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